The University of Dundee is working with partners around the world as part of an expanding effort to rapidly repurpose existing drugs against Covid-19.
An international research network established by Scripps Research centres around ReFRAME, the world’s leading collection of drugs known to be safe in humans.
The network of collaborating scientific laboratories is aiming to leverage ReFRAME to find antiviral compounds against the novel coronavirus.
Researchers at Calibr, the drug development division of Scripps Research, are teaming up with scientists from the United States, Europe and Asia to screen the vast collection of compounds for individual drugs or combinations that may be effective in treating people exposed to Covid-19.
“Covid-19 is an unprecedented public health crisis that will only be brought fully under control by effective medical therapies,” said Peter Schultz, PhD, president and CEO of Scripps Research. “Repurposing drugs that have already been approved for use in humans, or compounds for which we have ample safety data, offers the most rapid path to finding an antiviral drug or drug combination that is effective against Covid-19.”
Professor David Gray, Head of Biology and Professor of Translational Biology at the University of Dundee’s Drug Discovery Unit, is part of the international collaboration.
Professor Gray said, “This is an excellent example of the international research community coming together quickly to try and find drugs that could be rapidly developed for use against Covid-19. It is the combination of expertise from around the world that will give us our best chance of finding drugs that can be used to successfully treat or control Covid-19.”
Dundee’s involvement in the project also extends to Professor Andrew Hopkins and the pharmaceutical company Exscientia, a spin-out from the University.
Calibr established the ReFRAME collection in 2018 with support from the Bill & Melinda Gates Foundation to tackle areas of urgent unmet medical need, especially neglected tropical diseases. The collection has since grown to comprise over 13,000 compounds, and drugs have already been identified that are being repurposed for a number of diseases.
Calibr also developed an open source database containing preclinical and clinical data on these drugs. With such well-characterized therapeutic properties, the compounds can be rapidly screened and advanced into a patient setting, without many of the steps typically required before new drugs can reach that stage.
ReFRAME is highlighted in the Covid-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation. Together, Calibr and the Gates Foundation are working to establish collaborations with leading pharma companies to further augment ReFRAME’s collection of antiviral compounds for future pandemic response.
Because ReFRAME was established well before the COVID-19 crisis, Calibr scientists were able to quickly mobilise to begin screening the collection for activity against SARS-CoV-2, the virus that causes the disease. These experiments, which test hundreds or thousands of compounds at a time, seek to identify drugs that prevent the virus from entering, infecting or replicating in human cells. Researchers are also screening for compounds that could be taken in combination with other drugs to improve the efficacy of antivirals such as remdesivir, a Gilead drug currently being tested in five Covid-19 clinical trials.
Soon after the initial Covid-19 outbreak began, Calibr began sharing the ReFRAME library and conducting joint experiments with other research teams at Scripps Research and collaborating institutions worldwide. They are now working on dozens of projects with laboratories in the United States and abroad, combining Calibr’s drug discovery and screening expertise with collaborators’ deep knowledge of infectious disease biology.
Many of Calibr’s collaborators are experts in virology and antiviral therapeutics, with several projects focused on finding drugs that prevent SARS-CoV-2 viral replication—the process by which a virus hijacks a cell’s genetic machinery to create copies of itself. Collaborators on these projects include Johan Neyts, PhD, at Rega Institute for Medical Research in Belgium; Matthew Frieman, PhD, at University of Maryland Medical School in Maryland; Sumit Chanda, PhD, at Sanford Burnham Prebys Medical Discovery Institute in California; Adolfo Garcia-Sastre, PhD, at Mount Sinai in New York; and Dennis Burton, PhD, and Tom Rogers, MD, PhD, at Scripps Research.
In addition, Calibr has formed COVID-19 drug screening collaborations with other U.S. researchers including Wes Van Voorhis, MD, PhD, at University of Washington; Richard Whitley, MD, at University of Alabama at Birmingham; John Malona, PhD, at Jnana Therapeutics in Boston; David Ho, MD, Columbia University; Pei-Yong Shi, University of Texas Medical Branch; and Scripps Research professors Michael Farzan, PhD, David Nemazee, PhD, and Stefano Forli, PhD.
Collaborators outside the United States include David Gray, PhD, at University of Dundee, and Andrew Hopkins, PhD, at the pharmaceutical company Exscientia, both in the United Kingdom; Thomas Pietschmann, PhD, at Helmholtz Center for Infection Research, Germany; and Ren Sun, PhD, at Hong Kong University, in China.
Arnab Chatterjee, vice president of medicinal chemistry at Calibr, says the power of the ReFRAME drug collection is how it enables Calibr to quickly partner with leading research teams to develop precise and rapid screens against a wide range of diseases.
“In the case of COVID-19, we can leverage this important resource, along with Calibr’s expertise in drug development and discovery, to collaborate with some of the world’s leading virology labs and quickly identify potential medicines,” said Chatterjee. “While the results are still preliminary and need to be confirmed, we have already identified a number of compounds that show varying degrees of activity against the virus.”
Schultz says that once these results are confirmed they hope to begin testing the drugs in vivo and testing combinations of drugs that work by two different mechanisms for improved enhanced effectiveness.